The nature and rate of redistribution of bound platinum among plasma proteins are to be studied. Also, the effectiveness of small sulfur-containing nucleophiles such as methionine in the displacement of platinum from plasma proteins and from kidney tissue of rats will be evaluated as a possible approach to reducing therapeutically inactive and potentially toxic residual platinum levels following therapy. From the data obtained during the course of these studies it is anticipated that in vivo fate of cisplatin will be better understood. Research and development of more sophisticated analytical methodology for separation and quantitation of cisplatin and its various biotransformation products will be pursued concurrently with the chemical studies. Included in this phase of the work is the development of an on-line reaction detector for use in conjunction with chromatographic separations. Such an advance in analytical methodology would be of great value in addressing the chemistry and the clinical pharmacokinetics of cisplatin and second generation platinum and the clinical pharmacokinetics of cisplatin and second generation platinum analogs.